1. Field of the Invention
The present invention relates to oral salmon calcitonin pharmaceuticals, to methods of enhancing bioavailability of orally administered salmon calcitonin, and to methods of treating bone and calcium disorders in humans by orally administering salmon calcitonin in accordance with the invention.
2. Description of the Related Art
Salmon calcitonin is a peptide hormone which decreases uptake of calcium from bone. When used to treat bone-related diseases and calcium disorders (such as osteoporosis, Paget's disease, hypercalcemia of malignancy, and the like), it has the effect of helping maintain bone density. Many types of calcitonin have been isolated (human calcitonin, salmon calcitonin, eel calcitonin, elkatonin, porcine calcitonin, and chicken calcitonin). There is significant structural non-homology among the various calcitonin types. For example, there is 50% percent identity between the amino acids making up human calcitonin and those making up salmon calcitonin.
Salmon calcitonin used in the prior art has usually been administered by injection or by nasal administration. However, these modes of administering the calcitonin are significantly less convenient than, and involve more patient discomfort than, oral administration. Often this inconvenience or discomfort results in substantial patient noncompliance with a treatment regimen. However, the prior art is not believed to have reported an ability to achieve reproducible blood levels of salmon calcitonin when administered orally. This is believed to be because salmon calcitonin lacks sufficient stability in the gastrointestinal tract, and tends to be poorly transported through intestinal walls into the blood.
Proteolytic enzymes of both the stomach and intestines may degrade salmon calcitonin, rendering it inactive before the calcitonin can be absorbed into the bloodstream. Any amount of salmon calcitonin that survives proteolytic degradation by proteases of the stomach (typically having acidic pH optima) is later confronted with proteases of the small intestine and enzymes secreted by the pancreas (typically having neutral to basic pH optima). Other difficulties arising from the oral administration of salmon calcitonin involve the relatively large size of the molecule, and the charge distribution it carries. This may make it more difficult for salmon calcitonin to penetrate the mucus along intestinal walls or to cross the intestinal brush border membrane into the blood. These additional problems may further contribute to the limited bioavailability of salmon calcitonin.